1. Field of the Invention
The invention relates to a process for preparing microcapsule reagents suitable for immunological response, more particularly, to a process for preparing microcapsule reagents suitable for an antigen-antibody response which have high sensitivity, are stable and cause non-specific agglutination only with difficulty.
2. Development of the Invention
In order to facilitate an antigen-antibody response of high sensitivity in a simple manner, an immunological agglutination method in which an antigen or antibody is carried on a water-insoluble carrier and which causes agglutination based on an antigen-antibody response which can be seen with the naked eye has been employed.
Red blood cells of animals such as chickens, alligators, sheep, etc., have been used as carriers for the antigens or antibodies and, utilizing these carriers, passive heamagglutination (PHA) has generally been used since this method provides high sensitivity with simple operations.
Recently, a method has been used for semi-qualitatively determining the presence or absence of antigens or antibodies very efficiently in a simple manner which is called the microtiter system. However, the microtiter system involves disadvantages, e.g., due to the use of animal-originated carriers, red cell carriers per se are antigenic and often cause specific agglutination to adversely affect the desired antigen-antibody response: further, efficiency is not uniform based on differences between subjects, changes with the passage of time and cost is high.
A latex agglutination method in which a polystyrene latex is used as a carrier has also been put into practical use. While the disadvantages encountered with the use of animal-originated carriers is eliminated by this method, this method also involves disadvantages, e.g., not only is sensitivity poor as compared to the passive haemagglutination method, but storability over long periods of time is poor because of weak bonding with an antigen or antibody. Further, natural agglutination--not based on an antigen-antibody response--tends to occur, etc.
In U.S. Pat. No. 4,342,739, microcapsules are suggested for use in place of conventional carriers for immune substances, such as the aforesaid red cells, latexes, etc., for antigen-antibody agglutination. In the case microcapsules are employed as carriers, a marked improvement in sensitivity and accuracy is generally recognized in the detection of various antibodies or antigens in specimens based on antigen-antibody agglutination. This is due to the fact that microcapsules having a desired specific gravity of 0.8 to 1.20, preferably 1.07 to 1.16, can be prepared in a desired particle size range of 0.1 to 30 microns, preferably 0.5 to 10 microns, by suitably choosing the core substance(s) of the microcapsules. The microcapsules proposed in U.S. Pat. No. 4,342,739 are not charged (zero charge) or are positively charged in the acidic pH area.
However, some antigens or antibodies are sensitized only with extreme difficulty and a method for preparing reagents capable of utilizing such antigens or antibodies has long been desired in the art.